Mechanistic Insights from the NTP Studies of Chromium

Hexavalent chromium (Cr(VI)) is a contaminant of water and soil and is a human lung carcinogen. Trivalent chromium (Cr(III)), a proposed essential element, is ingested by humans in the diet and in dietary supplements such as chromium picolinate (CP). The National Toxicology Program (NTP) demonstrate...

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Bibliographic Details
Published in:Toxicologic pathology 2013-02, Vol.41 (2), p.326-342
Main Authors: Witt, Kristine L., Stout, Matthew D., Herbert, Ronald A., Travlos, Gregory S., Kissling, Grace E., Collins, Bradley J., Hooth, Michelle J.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carcinogenicity Tests
Chemical and industrial products toxicology. Toxic occupational diseases
Chromium - chemistry
Chromium - pharmacokinetics
Chromium - toxicity
Duodenum - drug effects
Duodenum - pathology
Female
Histiocytes
Hyperplasia - chemically induced
Liver - drug effects
Liver - pathology
Lymph Nodes - drug effects
Lymph Nodes - pathology
Male
Medical sciences
Metals and various inorganic compounds
Mice
Mouth Mucosa - drug effects
Mouth Mucosa - pathology
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Mutagenicity Tests
Neoplasms - chemically induced
Rats
Tissue Distribution
Tongue - drug effects
Tongue - pathology
Toxicology
Tumors
Water Pollutants, Chemical - chemistry
Water Pollutants, Chemical - pharmacokinetics
Water Pollutants, Chemical - toxicity
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Summary:Hexavalent chromium (Cr(VI)) is a contaminant of water and soil and is a human lung carcinogen. Trivalent chromium (Cr(III)), a proposed essential element, is ingested by humans in the diet and in dietary supplements such as chromium picolinate (CP). The National Toxicology Program (NTP) demonstrated that Cr(VI) is also carcinogenic in rodents when administered in drinking water as sodium dichromate dihydrate (SDD), inducing neoplasms of the oral cavity and small intestine in rats and mice, respectively. In contrast, there was no definitive evidence of toxicity or carcinogenicity following exposure to Cr(III) administered in feed as CP monohydrate (CPM). Cr(VI) readily enters cells via nonspecific anion channels, in contrast to Cr(III), which cannot easily pass through the cell membrane. Extracellular reduction of Cr(VI) to Cr(III), which occurs primarily in the stomach, is considered a mechanism of detoxification, while intracellular reduction is thought to be a mechanism of genotoxicity and carcinogenicity. Tissue distribution studies in additional groups of male rats and female mice demonstrated higher Cr concentrations in tissues following exposure to Cr(VI) compared to controls and Cr(III) exposure at a similar external dose, indicating that some of the Cr(VI) escaped gastric reduction and was distributed systemically. The multiple potential pathways of Cr-induced genotoxicity will be discussed.
ISSN:0192-6233
1533-1601
DOI:10.1177/0192623312469856